Causal Relationship Between Immune Cells and Hypopituitarism: Bidirectional Mendelian Randomization Study.

Abstract

Hypopituitarism, one or more pituitary hormones inefficiently produced by the anterior pituitary or released from the posterior pituitary to adapt to the needs of the organism. Existing epidemiological data show that immune-mediated diffuse infiltration of the anterior pituitary is important in the development of hypopituitarism. However, the precise connection between immune cells and hypopituitarism remains unclear. This study aimed to elucidate the potential causal links between the 731 immune cell types and hypopituitarism risk. Based on data from a genome-wide association study, a bidirectional two-sample Mendelian randomization analysis was performed using 5 methods to explore the potential influence of immune cell phenotypes on hypopituitarism. Sensitivity analyses were conducted to examine the robustness of these findings. Our findings support that B cells, T cells, Tregs, dendritic cells, monocytes, and myeloid cells each have a bidirectional influence on hypopituitarism. One B-cell phenotype was associated with increased hypopituitarism risk, while 2 B-cell phenotypes play a protective role in hypopituitarism. Moreover, 7 T-cell phenotypes demonstrate significant protective properties on hypopituitarism. Seven Tregs were associated with increased hypopituitarism risk. Furthermore, one monocyte was identified to be significantly associated with hypopituitarism risk. In addition, reverse Mendelian randomization analysis revealed that hypopituitarism was positively associated with 30 additional immune cell phenotypes and negatively associated with 17 immune cells. Our investigation shed light on the intricate potential relationship between immune cells and hypopituitarism via genetic methods, underscoring the immune-mediated pathway in hypopituitarism pathogenesis, thereby offering valuable insights for future clinical investigations.